Evidence shows cruciferous vegetables exhibit chemoprotective properties, commonly attributed to their rich source of isothiocyanates. However, epidemiological data examining the association between cruciferous vegetable intake and colorectal neoplasms have been inconclusive. This meta-analysis examines the epidemiological evidence to characterize the association between cruciferous vegetable intake and risk of developing colorectal neoplasms. Thirty-three articles were included in the meta-analysis after a literature search of electronic databases. Subgroup analysis for individual cruciferae types (n = 8 studies) and GST polymorphism (n = 8 studies) were performed. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated. Results show a statistically significant inverse association between cruciferous vegetable intake and colon cancer [OR = 0.84; 95% confidence interval (CI): 0.72-0.98; P value heterogeneity < 0.001]. Broccoli in particular exhibited protective benefits against colorectal (CRC) neoplasms (OR = 0.80; 95% CI: 0.65-0.99; P value heterogeneity = 0.02). Stratification by GST genotype reveals that the GSTT1 null genotype confers a reduction in CRC risk (OR = 0.78; 95% CI: 0.64-0.95; P value heterogeneity = 0.32). This study provides support to the hypothesis that cruciferous vegetable intake protects against cancer of the colon. This study also demonstrates the significance of gene-diet interactions and the importance of assessing individual cruciferous vegetables.